HMGB1 and metabolic pathways in Acinetobacter baumannii pneumonia: an associative study.

BACKGROUND

Acinetobacter baumannii (AB) pneumonia often leads to lung injury and multisystem dysfunction. High Mobility Group Box 1 (HMGB1) is known to play a crucial role in the progression of AB. In this study, we aimed to investigate the association between HMGB1 levels and the severity of AB pneumonia.

METHODS

We conducted a study with a total of 91 participants, divided into three groups: patients with AB infection (n = 44), patients with AB complicated multiple organ disfunctions (MODs) (n = 19), and healthy controls (n = 28). Clinical parameters were assessed, HMGB1 levels were measured, and metabolomic analysis was performed. Validation experiments were conducted using SD rats.

RESULTS

Patients with AB exhibited significantly elevated levels of HMGB1. In the multi-organ failure group, neutrophils, monocytes, and HMGB1 levels were higher, while lymphocytes were reduced. Metabolomic analysis revealed 28 metabolites correlated with HMGB1, among which 12-HPETE, asparagine, lactic acid, and carbamyl-aspartate showed the most notable changes. These representative metabolites reflect HMGB1-associated shifts in inflammation and energy metabolism. HMGB1 elevation was further confirmed in SD rats, and its blockade alleviated lung inflammation. Consistently, C-reactive protein (CRP) and procalcitonin (PCT) levels were also increased, supporting the link between HMGB1 and systemic inflammation.

CONCLUSION

HMGB1 levels rise sharply in AB pneumonia-especially in patients with MODs-and correlate with inflammatory and hypoxic metabolic shifts. Anti-HMGB1 treatment in SD rats reduced lung inflammation and injury, highlighting HMGB1's potential as a diagnostic biomarker and therapeutic target.